Abstract
Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls.We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function.Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated i n cis with gene expression at ACKR2 and DGKQ Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium.CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.
Highlights
Asthma is a chronic inflammatory disease of the airways, characterised by variable airflow obstruction associated with symptoms of wheezing, shortness of breath, chest tightness and coughing
In order to identify molecular mechanisms related to asthma remission in the airways, we investigated whether variation in DNA methylation in bronchial biopsies is associated with remission of asthma
We found four individual CpG-sites and 42 regions to be differentially methylated between subjects in remission and persistent asthmatics
Summary
Asthma is a chronic inflammatory disease of the airways, characterised by variable airflow obstruction associated with symptoms of wheezing, shortness of breath, chest tightness and coughing. The average remission rate of asthma is ∼2% per year, with a higher chance to go into remission with an earlier onset of asthma, less severe airway obstruction and cessation of smoking [3, 4]. A subset of patients with asthma in remission still have airway obstruction and/or show airway hyperresponsiveness (AHR) in provocation tests [5]. Clinical remission is defined as the absence of asthma symptoms and no use of asthma medication. Complete remission of asthma is defined as the absence of asthma symptoms, no use of asthma medication, normal lung function and no AHR
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